Study Purpose:

To determine the effect of repeated intravenous injection of a monoclonal antibody, directed at the inflammatory cytokine tumor necrosis factor (TNF), on the mood of patients diagnosed with treatment-resistant depression (TRD); to note the effects of the intervention on the levels of inflammatory cytokines and high-sensitivity C-reactive protein (hs-CRP) and concentrations of TNF

Intervention Characteristics/Basic Study Process:

Patients were randomized to receive either placebo or infliximab infusions of 5 mg/kg at baseline and at weeks 2 and 6. Assessments of clinical and inflammatory status (hs-CRP, TNF, and its soluble receptors I and II) were conducted at baseline and at weeks 1–4, 6, 8, 10, and 12.

Sample Characteristics:

The sample was composed of 60 participants; 30 were in the placebo group and 30 were in the infliximab group.

The age range of participants was 25–60 years.

Of male participants, 33% were treated with infliximab and 33% were treated with placebo. Of female participants, 67% were treated with infliximab and 67% were treated with placebo.

All participants were moderately resistant to treatment in the current episode, having depression of moderate severity as measured by the treatment resistance staging method and a self-report of symptoms of depression. Group assignment was stratified by gender and by hs-CRP level (< 2 or ≥ 2).

Of all participants, 77% were white, 20% were black, and 97% were college-educated (that is, had a college education ranging from some college to the attainment of a graduate degree). The groups were evenly matched in terms of approximate age at the time of the diagnosis of major depression, number of episodes of major depression to date, and antidepressant trials in the current episode. Authors noted no significant differences in the two test groups.

Setting:

Single site

Outpatient

Emory University, Division of Digestive Diseases, Atlanta, Georgia

Phase of Care and Clinical Applications:

Transition phase after active treatment

Study Design:

Randomized double-blind placebo-controlled trial

Measurement Instruments/Methods:

Self-report

Hamilton Rating Scale for Depression (HRSD, which the authors referred to as HAM-D; clinical response defined as at least 50% reduction in HAM-D score) and the Clinical Global Impression-Severity (CGI-S) scale

Measures of hs-CRP, TNF, and TNF soluble receptors I and II

Results:

There were no differences in HAM-D score changes over time between groups. These scores declined significantly over time in both groups (p = 0.01). Subgroup analysis showed that, for patients with baseline hs-CRP concentration greater than 5 mg/L, those on infliximab had greater improvement in HAM-D scores (effect size = 0.41). Treatment response rates were not different between groups

Conclusions:

Treatment with infliximab is not an effective intervention for treatment-resistant depression. However, as levels of hs-CRP increase, infliximab has greater effect. Antagonism of TNF is ineffective against treatment-resistant depression. More research is needed to determine inflammatory biomarkers in patients who may uniquely respond to immune-targeted therapies.

Limitations:

The study had a small sample size, with fewer than 100 participants.

The study had a risk of bias due to no control.

Nursing Implications:

This study yields no results that can immediately be applied to practice. Nurse-researchers should consider constructing and implementing clinical trials aimed at exploring, developing, and understanding inflammatory biomarkers to identify immune-targeted therapeutic interventions.